8q Gain Has No Additional Predictive Value in SF3B1MUT Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with BAP1MUT Uveal Melanoma

Josephine Q N Nguyen; Wojtek Drabarek; Jolanda Vaarwater; Serdar Yavuzyigitoglu; Robert M Verdijk; Dion Paridaens; Nicole C Naus; Annelies de Klein; Erwin Brosens; Emine Kiliç; Rotterdam Ocular Melanoma Study group

doi:10.1016/j.xops.2023.100413

8q Gain Has No Additional Predictive Value in SF3B1^MUT Uveal Melanoma but Is Predictive for a Worse Prognosis in Patients with BAP1^MUT Uveal Melanoma

Ophthalmol Sci. 2023 Oct 16;4(2):100413. doi: 10.1016/j.xops.2023.100413. eCollection 2024 Mar-Apr.

Authors

Collaborators

Rotterdam Ocular Melanoma Study group:
Emine Kilic, Annelies de Klein, Erwin Brosens, Nicole C Naus, Dion Paridaens, Serdar Yavuzyigitoglu, Wojtek Drabarek, Josephine Qn Nguyen, Jolanda Vaarwater, Robert M Verdijk

Affiliations

¹ Department of Ophthalmology, Erasmus MC Cancer Institute, Erasmus MC Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
² Department of Clinical Genetics, Erasmus MC Cancer Institute, Erasmus MC Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
³ Department of Ophthalmic Oncology, The Rotterdam Eye Hospital, 3011 BH, Rotterdam, The Netherlands.
⁴ Department of Pathology, Section Ophthalmic Pathology, Erasmus MC Cancer Institute, Erasmus MC Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands.
⁵ Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.

Abstract

Purpose: Gain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in the absolute number of 8q-copies correlated with an even shorter survival. Splicing factor 3b subunit 1 (SF3B1)-mutated (SF3B1^MUT) tumors display structural chromosomal anomalies and frequently show a partial gain of chromosome 8qter. A recent subset of SF3B1^MUT UM with early-onset metastases has been identified, prompting the investigation of the relationship between survival, 8q gain, and SF3B1^MUT UM.

Design: Retrospective cohort study.

Subjects: Patients diagnosed with UM who underwent enucleation or received a biopsy at the Erasmus MC Cancer Institute or the Rotterdam Eye Hospital, The Netherlands were included.

Methods: Fifty-nine patients with SF3B1^MUT tumors and 211 patients with BRCA1 associated protein 1 (BAP1)-mutated (BAP1^MUT) tumors were included in this study. Copy number status and gene expression were assessed using either a single nucleotide polymorphism array, fluorescence in situ hybridization, and karyotyping, or a combination of these techniques. Disease-free survival was determined and a cut-off of 60 months was used to define early-onset metastatic disease.

Main outcome measures: Disease-free survival.

Results: Forty-eight patients with SF3B1^MUT UM (81%) had chromosome 8q gain (3 copies, 78%; 4 copies, 22%). Kaplan-Meier analysis of SF3B1^MUT UM did not indicate a difference in survival in patients with or without gain of 8q (P = 0.99). Furthermore, the number of 8q copies was not associated with survival when comparing early (P = 0.97) versus late (P = 0.23) metastases group. In contrast, the presence of 8q gain (86%) was correlated with a decreased survival in BAP1^MUT UM (P = 0.013).

Conclusions: We did not find a correlation between 8q gain and early-onset metastasis in SF3B1^MUT tumors. Gain of 8q has no additional predictive value in SF3B1^MUT tumors. In contrast, 8q gain is predictive of a worse prognosis in patients with BAP1^MUT tumors. Thus, gain of chromosome 8q has additional predictive value for BAP1^MUT tumors, but not for SF3B1^MUT tumors.

Financial disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keywords: Aberration; Chromosome 8q gain; Copy number variation; Prognosis.